Skin Biopsy Research Articles

Application of Targeted Optical Coherence Tomography in Oral Cancer: A Cross-Sectional Preliminary Study

Background/Objectives: The diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) represent a significant challenge in oral medicine. Optical coherence tomography (OCT) shows promise for evaluating oral tissue microstructure but lacks standardized diagnostic protocols tailored to the structural variability and lesions of oral mucosa. Methods: This cross-sectional observational study aims to evaluate the diagnostic accuracy of targeted biopsy-based and site-coded OCT protocols for common OPMDs and OSCC. Adult patients clinically diagnosed with OPMDs, including oral leukoplakia (OL), oral lichen planus (OLP), and OSCC were enrolled. Clinical and OCT evaluation before and after punch scalpel-site registration preceding diagnostic biopsy on the target site was performed. Blinded observers analyzed the OCT scans for OCT-based diagnoses. Sensitivity, specificity, and diagnostic accuracy for OCT evaluations before and after punch scalpel-site registration were statistically compared with histological findings. Results: A dataset of 2520 OCT scans and 210 selected images from 21 patients was obtained. Sensitivity and specificity post-target site registration were high for OSCC (98.57%, 100.00%), OL (98.57%, 98.57%), and OLP (97.14%, 98.57%). The positive predictive values ranged from 97.14% to 100.00%, while negative predictive values ranged from 98.57% to 99.29%. Inter-observer agreements were strong for OSCC (0.84) and moderate for OL (0.54) and OLP (0.47–0.49). Targeted OCT scans significantly improved diagnostic accuracy for all conditions (p < 0.001). Conclusions: This preliminary study supports using site-targeted OCT scans followed by a site-targeted punch biopsy, enhancing precision in oral diagnostics. This approach is foundational for developing pioneering automated algorithms guiding oral cancer and pre-cancer diagnosis via OCT imaging.

Rocky Mountain Spotted Fever Encephalitis and "Starry Sky" Pattern on MRI: A Case Report.

Rocky Mountain Spotted Fever (RMSF) is a tick-borne disease caused by Rickettsia rickettsii (R. rickettsii). RMSF presents after a tick bite with fever, rash, and headache but can also cause more serious neurological manifestations. We report a case of RMSF encephalitis presenting with altered sensorium and rapid progression to coma, fever, and petechial rash, and an magnetic resonance imaging (MRI) brain notable for a "starry sky" pattern. A 61-year-old woman presented with confusion and fever and was diagnosed with a urinary tract infection. Two days later, she became comatose. MRI brain revealed lacunar infarcts in the right centrum semiovale and splenium of the corpus callosum. Lumbar puncture was notable for neutrophilic pleocytosis and elevated protein with negative bacterial and viral cultures. Empiric meningitis therapy was initiated, and she was transferred to our institution. On transfer, she was febrile, comatose, and had a diffuse petechial rash. Repeat MRI brain demonstrated diffuse, innumerable punctate foci of diffusion restriction with susceptibility-weighted signal attenuation throughout cerebral hemispheres in a "starry sky" pattern. Skin biopsy revealed perivascular lymphocytic infiltrates. Serologic RSMF antibody titers were obtained, and doxycycline was initiated for presumed RMSF encephalitis. The family opted to pursue palliative measures, given no clinical improvement. RSMF titers and postmortem PCR from brain tissue were positive for R. rickettsii. This case report highlights the clinical presentation of RMSF encephalitis. RMSF encephalitis should be suspected in a patient presenting with encephalopathy, fever, petechial rash, and MRI brain findings of diffuse punctate foci of diffusion restriction and susceptibility-weighted signal attenuation in a "starry-sky" pattern.

An injectable hydrogel of porcine cholecyst extracellular matrix for accelerated wound healing.

Hydrogel formulations of xenogeneic extracellular matrices have been widely used for topical wound care because of their exceptional tunability over other formulations like lyophilized sheets, powders, non-injectable gels, pastes, and ointments. This is important in the treatment of wounds with irregular shapes and depth. This study identified an injectable hydrogel formulation of porcine cholecyst extracellular matrix (60%) in medical-grade carboxymethyl cellulose (40%) as vehicle and evaluated its biomaterial properties. Further, an in-depth evaluation of in vivo wound healing efficacy was conducted in a rat full-thickness skin excision wound healing model, which revealed that the hydrogel formulation accelerated wound healing process compared to wounds treated with a commercial formulation and untreated wounds. The hydrogel appeared to have promoted a desirable pro-regenerative tissue reaction predominated by Th2 helper lymphocytes and M2 macrophages as well as an effective collagen remodeling indicative of diminished scarring. In conclusion, the porcine cholecyst extracellular matrix injectable hydrogel formulation appeared to be a promising candidate formulation as an advanced wound care biomaterial for faster healing of skin wounds with minimal scarring.

Clinicopathological study of 24 cases of monkeypox virus infection-related rashes

Objective: To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests. Methods: Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope® hybridization and electron microscopy. Results: All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri's bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope® hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions: The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

Diagnostic Challenge of Lupus with Overlap Syndrome in an Adolescent: A Case Report

Lupus with overlap syndrome is an uncommon autoimmune disease that typically affects teenage females. It can present as various symptoms affecting multiple organs. Delay in the diagnosis of lupus will lead to deleterious effects on the implicated adolescents’ health. The case report aims to describe the diagnostic challenge of a refractory skin disease leading to a delay in diagnosis and highlight its psychosocial impact. Here, we describe a case of a teenager who presented with poorly controlled chronic dermatitis. The chronic dermatitis was refractory to the first-line therapy of topical steroids and emollients. She was finally diagnosed with lupus and overlap syndrome, confirmed by a skin biopsy. In conclusion, any chronic refractory skin diseases warrant further referral and investigation at the tertiary centre. Assessment of psychosocial in managing chronic skin disease in adolescent is essential as it could implicate their mental health further.

Molecular detection of lumpy skin disease virus in naturally infected cattle and buffaloes: unveiling the role of tick vectors in disease spread.

Lumpy skin disease (LSD) is a viral disease that affects cattle and buffaloes in Egypt, causing considerable economic losses in the animal sector. This study aimed to investigate the recent outbreak of LSDV in cattle and buffaloes and evaluate the potential role of the hard tick Rhipicephalus annulatus in their transmission through isolation and molecular characterization by multiplex PCR (mPCR) and real-time quantitative PCR (rt-qPCR) assays. A total of 50 skin biopsies (cattle n = 30, buffaloes n = 20), 110 nasal swabs (cattle n = 76, buffaloes n = 44), and 129 blood samples (cattle n = 84, buffaloes n = 45) were collected. In addition, 145 hard ticks of different stages were collected from cattle and buffaloes of different breeds and ages in different governorates in Egypt from November 2021 to June 2022. Multiplex PCR and real-time quantitative PCR (rt-qPCR) assays based on SYBR Green and targets (P32, VP32, G protein, and viral fusion protein) were used. We identified positive results in 17 out of 30 cattle skin biopsies (56.6%), 1 out of 7 buffalo skin scabs (14.3%), and 5 out of 45 buffalo blood samples (11.11%) using mPCR and RT-qPCR methods. We successfully isolated LSDV from hard ticks and cattle infested with ticks and exhibited characteristic signs of LSD on the chorioallantois membrane (CAM) of specific pathogen-free embryonated chicken eggs (SPF-ECE). The isolates were confirmed by multiplex PCR and RT-qPCR. The cyclic threshold (Ct) with correlation-slandered curve values of rt-qPCR ranging from 10.2 to 36.5 showed the amount of LSDV-DNA in different samples. The study's findings demonstrated the widespread circulation of LSDV in both cattle and buffaloes in Egypt and provided strong evidence that hard ticks R. annulatus play a role in the transmission of LSDV in susceptible animals.

DRESS Syndrome That Resembles Graft-Versus-Host Disease after Chemotherapy in a Pediatric Patient: A Case Report

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening, drug-induced adverse reaction characterized by skin eruptions, lymphadenopathy, fever, and a broad range of other bodily manifestations. The spectrum of histopathologic and clinical presentations is wide; therefore, DRESS syndrome can mimic other diseases. Case Presentation: We present a case of a 4-year-old male patient who started chemotherapy with vincristine, cytarabine, and etoposide. The first clinical signs were fever, hemodynamic in-stability, and maculopapular erythema. Biopsies of skin lesions were taken, and hyperkeratosis, focal parakeratosis, acanthosis with slight spongiosis, and intraepithelial dyskeratotic cells were observed. There was a perivascular lymphoid infiltrate with abundant eosinophils in the dermis, and eosinophil permeations to the acrosyringium and epithelium were found. Conclusion: DRESS syndrome is a drug-induced reaction that shares histopathological findings in skin biopsies with those seen in graft-versus-host disease. Although the histological findings are non-pathognomonic, they were characteristic enough to be of importance in the differential diagnosis.

Diagnosis and management of Rosai–Dorfman disease of the breast: Case report and literature review

AbstractRosai–Dorfman disease (RDD) is a rare subtype of non–Langerhans cell histiocytosis. It is a benign disease with variable presentations, with breast involvement being an uncommon manifestation. In this paper, we present a case of breast RDD in a 59‐year‐old Chinese woman who presented with a painless, enlarging mass in her right breast, accompanied by skin changes and no palpable axillary lymph node. A mammogram and breast ultrasonography revealed a progressively enlarging lesion with a suspicious axillary lymph node, leading to an upgrade from Breast Imaging Reporting and Data System (BIRADS) score of 3 to 4A on interval imaging. Core biopsy of the breast mass and cytology of the right axillary lymph node confirmed extranodal RDD. After a 5‐year period of observation, excision was performed due to persistent symptoms. Local recurrence of RDD, with skin discolouration and thickening, was confirmed by skin biopsy 1 year and 9 months after the operation. To the best of our knowledge, this is the first reported case of breast RDD in Hong Kong.

Attenuation of 1-chloro-2,4-dinitrobenzene-induced inflammation in atopic dermatitis-like skin lesions in rats by a pyrrole containing FELL-NH 2 bioconjugate: Cannabinoid receptor type 1 involvement

Atopic dermatitis (AD) is a chronic inflammatory skin condition of significant health and social importance, which justifies the search for new means of treatment. Since the endogenous cannabinoid system appears to be involved in the pathogenesis of AD, the proposed article summarizes the clinical impact on skin inflammation in a rat model of 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis-like condition after exogenous systemic administration of the cannabinoid receptor type 1 (CB1r) agonist anandamide, as well as after local treatment with a newly synthesized pyrrole moiety containing bioconjugate of FELL tetrapeptide with CB1r-dependent analgesic activity. The changes in skin lesions and ear thickness were estimated along with the CB1r expression immunohistochemically determined on skin punch biopsies. The results showed attenuation of skin lesions by anandamide and lack of positive effect after introduction of CB1r antagonist, accompanied by a change in CB1r expression, suggesting the involvement of the cannabinoid system in the defensive functions of the skin. The topically applied newly synthesized bioconjugate also favorably affected skin manifestations of inflammation, but without a change in CB1r expression, suggesting the involvement of other mechanisms in the reported effects.

Validation of the performance of a point of care molecular test for leprosy: From a simplified DNA extraction protocol to a portable qPCR.

The study aimed to optimize qPCR reactions using oligonucleotides from the first Brazilian molecular diagnostic kit for leprosy on a portable platform (Q3-Plus). In addition, we sought to develop a simplified protocol for DNA extraction that met point-of-care criteria. During optimization on the Q3-Plus, optical parameters, thresholds, and cutoffs for the 16S rRNA and RLEP targets of M. leprae were established using synthetic DNA, purified DNA from M. leprae, and pre-characterized clinical samples. For the simplified extraction protocol, different lysis solutions were evaluated using chaotropic agents, and purification was carried out by transferring the lysed material to FTA cards. The complete protocol (simplified extraction + qPCR on the portable platform) was then evaluated with pre-characterized clinical skin biopsy samples and compared with standard equipment (QuantStudio-5). LOD95% for the optimized reactions was 113.31 genome-equivalents/μL for 16S rRNA and 17.70 genome-equivalents/μL for RLEP. Among the lysis solutions, the best-performing was composed of urea (2 M), which provided good dissolution of the skin fragment and a lower Ct value, indicating higher concentrations of DNA. The complete technological solution showed a sensitivity of 52% in reactions. Our results highlight the need for additional optimization to deal with paucibacillary samples, but also demonstrate the feasibility of the portable platform for the qPCR detection of M. leprae DNA in low infrastructure settings.

A Rare Case of Early Infantile Neuronal Ceroid Lipofuscinosis: Clinical and Diagnostic Insights

The Aim of the Study: The aim of this work is to show the different specific clinical and paraclinical aspects of ceroid lipofuscinosis in its early infantile form named Santavuori-Haltia disease through a new case.Given its rarety especially in consanguineous populations for better understanding the clinical presentation,progression and management of the disease. Introduction: The neuronal ceroid lipofuscinoses are a group of genetic brain diseases with an autosomal recessive manner characterized by the accumulation of an autofluorescent material in multiple tissues of patients. Clinically, they are progressive decline of mental and motor capacities, epilepsy and visual loss through retinal degeneration . In this work we report the early infantile neuronal ceroid lipofuscinosis or Santavuori-Haltia disease. Report Case: This is a 12-month-old infant from consanguineous parents who has presented with flexion spasms with eyelid clonia since the age of 1 month. The examination found microcephaly, and the neurological examination showed horizontal nystagmus with the absence of ocular pursuit and the presence of a pyramidal and extrapyramidal syndrome. Brain MRI shows delayed myelination. Skin biopsy confirms diagnosis. The Arg122Trp genetic mutation found is the most common one in this disease. Conclusion: Santaviori-Haltia disease is a rare and serious disease, the prognosis is severe, it must be mentioned in the face of psychomotor regression and a picture of encephalopathy. Confirmation of the diagnosis is based on histological and molecular biology data.

RUNX2 as a novel biomarker for early identification of patients progressing to advanced-stage mycosis fungoides

IntroductionThe majority of patients with mycosis fungoides (MF) have an indolent disease course, but a substantial fraction (20-30%) of patients progress to advanced stages – usually with a grave prognosis. Early differentiation between indolent and aggressive types of MF is important for the choice of treatment regimen and monitoring of the individual patient. Good biomarkers are therefore desired.MethodsHere, we used spatial transcriptomics on skin samples at time-of-diagnosis to enable prediction of patients who later progressed to advanced stages of MF. Formalin-fixed, paraffin-embedded skin biopsies at time of diagnosis from six patients with MF who progressed to advanced stages of disease within 4 months to 12 years after diagnosis, and nine patients who remained in early-stage disease over 9 to 27 years were analyzed using the GeoMx Digital Spatial Profiler to capture spatially resolved high-plex RNA gene expression data. Five different regions of interest (the epidermis, the basal layer of epidermis, CD4+ T-cells and neighboring cells, and Pautrier’s microabscesses) were profiled for further assessment.Results and discussionInterestingly, RUNX2, SHMT2, and MCM7 were upregulated in the enriched population of malignant T-cells in Pautrier’s microabscesses in patients who later developed advanced stages of disease. Expression of RUNX2, SHMT2 and MCM7 in malignant T-cells was confirmed in a subset of patients in MF skin using scRNA-seq datasets across multiple studies and correlating with stage of disease. Taken together, we provide first evidence that RUNX2 has potential as a biomarker to identify MF patients progressing to advanced stage disease. As RUNX2 has not previously been linked to MF, our data also shows the analytical strength of combining spatial transcriptomics with scRNA-seq analysis.

7877 Adipose Depot Differences In Regenerative Properties Of Exosomes Derived From Human Adipose Stem Cells

Abstract Disclosure: M.A. Krause-Hauch: None. R. Patel: None. B. Osborne: None. P. Albear: None. N.A. Patel: None. Many patients struggle with chronic recalcitrant wounds that are the result of delayed healing. Underlying inflammation is one major risk factor for impaired dermal wound healing that may lead to pathologies such as infection and scarring. Adult human adipose stem cells (hASCs) have shown tremendous potential in regenerative medicine. The regenerative potential of hASCs is dependent on secreted bioactive material which is packaged and released in extracellular exosomes. We previously showed that hASC exosomes from the subcutaneous depot (sc) promoted repair in human dermal fibroblasts using in vitro assays. In this study, we evaluated exosomes derived from the omental depot (om) of hASC and compared its efficacy with sc-hASC. Our results show differences in levels of the long noncoding RNA (lncRNA) cargo between om-hASCexo and sc-hASCexo. Next, we evaluated their repair potential in a wound model in vivo. Male and female F344 rats were dorsally wounded via punch biopsy and silicone scaffolding was attached to prevent contraction. The wounds were then either not treated (control) or treated with 50μg om-hASCexo or sc-hASCexo every alternate day when each wound size was measured for 1 week to monitor healing progress. After 7 days, wounds treated with either om-hASCexo and sc-hASCexo closed significantly faster than untreated control wounds. While no difference was observed in closure percentage after 7 days for wounds treated with either om-hASCexo and sc-hASCexo, sc-hASCexo appeared to act faster earlier (1-2 days post wound) in the wound healing process while om-hASCexo acts faster during later stages (2-4 days post wound) of wound healing. The wound tissue was collected for biochemical and histological analysis. qPCR analysis on day 7 revealed that both om-hASCexo and sc-hASCexo treatment resulted in increased levels of Collagen 1 & 3 and MMP9, while levels of TGF-β decreased with treatment. These results indicate that om-hASCexo and sc-hASCexo enhanced the wound healing process while decreasing inflammation of the wound. To determine the differences between om-hASCexo and sc-hASCexo treatments on wound healing pathways, RNAseq was performed. Results show specificity in pathway activation and gene expression between the om-hASCexo and sc-hASCexo treatments. In conclusion, we have demonstrated that the regenerative mechanisms differ between the hASC depots from which exosomes are secreted. At a broader level, this finding may shed light on the body’s organ health and repair processes in normal or disease states. Presentation: 6/3/2024

6942 Should there be a consensus statement about managing Inguinal Hernia In females? A Case of Delayed Diagnosis in Complete Androgen Insensitivity Syndrome (CAIS)

Abstract Disclosure: S. Echetebu: None. Introduction: Androgen Insensitivity Syndrome is usually due to a missense mutation that encodes part of the androgen receptor. More than 50% of females with CAIS present with inguinal hernias (4:1 female to male ratio). Previous CAIS studies have estimated the incidence of CAIS to be 0.8% to 2.4% in girls with inguinal hernias. 90% of the girls with CAIS will undergo inguinal hernia repair during childhood. The prevalence of germ cell tumors is estimated as 0.8% therefore, post-pubertal gonadectomy is now the recommended therapy for individuals with CAIS. Clinical Case: We present a case of a 15-year-old patient with primary amenorrhea who underwent bilateral inguinal hernia repair at the age of 5 weeks and was raised as a female. Initial ultrasound imaging at the age of 14 years revealed an absent uterus and complex hemorrhagic cysts of the ovaries. Further laboratory results revealed 46 XY chromosomal analysis, confirming her diagnosis of CAIS. Her laboratory values are: FSH 6.0 mIU/ml (1.0 to 18.6), Prolactin 15.6 ng/mL (<25), 17OHProgesterone 49 ng/dl (<265), Estradiol 30 pg/ml (<47), LH 17 mIU/ml (0.4 -11.7), Anti Mullerian Hormone 368 ng/ml (<13), Testosterone 629 ng/dl (<55 ). Upon our review of her past medical records from a different hospital, the operation note reports that her gonads resembled testes. Gonads were relocated in the abdomen without follow-up or consultation with an endocrinologist. Upon receiving her new diagnosis, the patient experienced significant emotional distress. As a result, both the patient and her family received psychological counseling and were referred to a genetic counselor to assess any potential risks for her younger sister. There is currently no consensus on the management of females with inguinal hernias in the available literature. It is widely accepted to perform gonadectomy. Currently, researchers at NIH are conducting an observational study on the benefits of additional delays in gonadectomy. Although most surgeons are familiar with this condition, it would be beneficial for families and patients to have an early diagnosis and provide appropriate education regarding future sexual encounters and fertility concerns. Conclusion: We propose to initiate a consensus statement for pediatricians, surgeons, and endocrinologists to perform systematic genetic testing in females with inguinal hernia. Such testing may include either a buccal mucosal smear, karyotype, or skin biopsy in all females with inguinal hernias. If the family chooses to delay orchiectomy, it is recommended that during hernioplasty, the testes should be repositioned in a location that allows for easy monitoring using annual imaging. By adopting this methodology, we can increase awareness about the effects of diagnosis and foster discussions among healthcare professionals regarding suitable management options. Presentation: 6/3/2024

7854 Ablation Aberration: A Case of Thyroid Dermopathy Exacerbation in a Filipino Male Following Radioactive Iodine Ablation and Total Thyroidectomy Improved by Weekly Intradermal Long-Acting Glucocorticoid Injection

Abstract Disclosure: K.T. Lim: None. O.C. Dampil: None. Ablation Aberration: A Case of Thyroid Dermopathy Exacerbation in a Filipino Male Following Radioactive Iodine Ablation and Total Thyroidectomy Improved by Weekly Intradermal Long-Acting Glucocorticoid Injection Introduction: Thyroid dermopathy (TD) represents an unusual extrathyroidal presentation of Graves' disease (GD), impacting about 0.5–4% of patients. RAI treatment for hyperthyroidism is known to progress Graves' ophthalmopathy. RAI-induced TD exacerbation, however, is rare in literature. Here, we present a case of worsening TD and ophthalmopathy in a Filipino patient with GD who underwent definitive therapy for persistent hyperthyroidism. Clinical Case: A 44-year-old man with GD had bilateral lower extremity indurated, mildly erythematous plaques for 4 years. Hyperthyroidism persisted despite methimazole compliance, so he underwent RAI ablation two years earlier, total thyroidectomy a year later, and has been on levothyroxine since. Despite definitive treatment, his extrathyroidal symptoms worsened. A punch biopsy of the skin lesions revealed upper and mid-lower dermis mucin deposition, with occasional spindle-shaped and stellate fibroblasts, and mast cells. These histopathologic findings were consistent with pretibial myxedema. We assessed his thyroid function and found he was euthyroid with normal TSH (3.1 μIU/mL; reference range 0.27-4.20) and an elevated TRAb (35.73 IU/L; reference range <1.75). Physical examination revealed thickened skin, cobblestone-like plaques, and non-pitting edema on the pretibial, ankle, and pedal areas. A 3.5-cm-diameter, circumscribed, orange-peel-textured, indurated plaque covered his left ankle. Fluocinolone acetonide 0.025% w/w ointment was initiated. After 3 weeks, his cutaneous symptoms improved by 35%, albeit his left ankle circumscribed plaque improved marginally. Triamcinolone acetonide 40 mg/mL was injected into this and other nodular lesions at 4mg (0.1 mL) per 1-cm-diameter circular region. Each dose was equally dispersed by multipoint intradermal injections using a 1 mL syringe with a 0.5”x 25G needle. A week after intralesional triamcinolone injection and continuous topical steroid application on the non-nodular lesions, a 70% improvement in cutaneous manifestations was observed (from baseline) with the plaques becoming thinner and softer. After three weekly intradermal steroid injections, the circumscribed plaque had flattened (with residual hyperpigmentation), and the other plaques and nonpitting edema dissipated. Conclusion: Our experience with this patient highlights a paradoxical TD exacerbation following RAI ablation and definitive surgery for persistent hyperthyroidism in GD. It also reveals that weekly administration of multiple subcutaneous injections of a long-acting glucocorticoid alleviates lesions where topical ointment does not. Presentation: 6/1/2024

7418 Xanthoma Disseminatum - A Rare cause of Diabetes Insipidus

Abstract Disclosure: P. Balasubramanian: None. J. Cohen: None. Z. Corbin: None. G. Panse: None. S.E. Inzucchi: None. Background: Xanthoma disseminatum is a rare non-Langerhans cell-derived benign histiocytosis of unknown etiology, characterized by mucocutaneous xanthomatosis. Systemic involvement occurs in a subset of patients, the most common manifestation being central diabetes insipidus in the setting of hypothalamic-pituitary- infundibulum infiltration, occurring in about 30-50% of the patients. We present the case of a man with biopsy proven cutaneous xanthoma disseminatum who developed central diabetes insipidus due to pituitary stalk involvement. Case Presentation: A 69-year-old male presented with a 2-year history of symmetrically distributed, erythematous to hyperpigmented macules and papules in the axillae and inguinal folds. He did not have any mucosal lesions. Skin biopsy revealed histiocytic infiltrate consistent with non-Langerhans cell histiocytosis, likely xanthoma disseminatum. He developed symptoms of polyuria and nocturia around the same time of the eruption, resulting in a large daily fluid intake of 100-120 ounces/day for several months. Laboratory evaluation revealed normal electrolytes. After an overnight water deprivation test, serum osmolality was 299mOsm/kg, serum sodium was 144mmol/L and urine osmolality was 280mOsm/kg, consistent with partial central diabetes insipidus. MRI pituitary with and without IV contrast showed thickening and hyperenhancement of the pituitary stalk. Anterior pituitary function was intact except for mild hypogonadotropic hypogonadism. He was started on DDAVP with good response and resolution of symptoms. Conclusion: Xanthoma disseminatum is characterized by extensive mucocutaneous xanthomatosis with occasional systemic involvement. The natural history of xanthoma disseminatum is usually benign, indolent, and slowly progressive with spontaneous regression described in a few cases. Hypothalamic and pituitary involvement may cause hyperprolactinemia, central diabetes insipidus, and variable degrees of hypopituitarism. Diabetes insipidus is often mild and sometimes transient. Occasionally, central diabetes insipidus can precede the skin lesions. Prognosis is generally good. Central nervous system involvement outside the hypothalamus/pituitary carries a poor prognosis. Presentation: 6/2/2024

8035 Severe Hyperglycemia Induced By Enfortumab Vedotin (EV) Treatment For Urothelial Carcinoma

Abstract Disclosure: N. Semreen: None. M.D. Goldberg: None. Introduction: Immunotherapy has revolutionized cancer treatment, but it has a wide range of adverse events including endocrinopathies. Here we present a case of severe hyperglycemia induced by enfortumab vedotin (EV) treatment for advanced urothelial carcinoma. Clinical Case: A 56-year-old male was admitted to our hospital with a painful rash in sun-exposed areas. He had metastatic urothelial carcinoma, with progression of disease after platinum-based chemotherapy, radiation therapy, and pembrolizumab, and had begun treatment with EV six weeks prior to presentation. He also had type 2 diabetes mellitus, with a recent A1c of 6.1% on metformin monotherapy, and obesity (BMI, 31 kg/m2). His blood glucose on admission was 600 mg/dL, and insulin therapy was initiated. There was no evidence for DKA or HHS. Over the course of his 9-day admission he required approximately 200 units of insulin per day to control his glucose. A fasting C-peptide level was 6.89 ng/mL (0.81-3.89 ng/mL) concurrent with a glucose of 181 mg/dL. Skin biopsy revealed erythema multiforme, which represented a grade 4 toxicity of EV treatment, and the EV was discontinued. Symptoms improved with oral glucocorticoids. The patient was discharged on multiple daily injections of insulin in addition to metformin. His insulin requirements fell rapidly, and one month later he was able to discontinue insulin completely. He was started on sacituzumab for his cancer treatment. Discussion: EV is a first-in-class antibody-drug conjugate directed against Nectin-4, which was approved in 2019 for previously treated locally advanced or metastatic urothelial carcinoma. Hyperglycemia was reported in 6.4% of patients receiving EV in the initial phase III study; BMI ≥ 30 kg/m2 and pretreatment A1c ≥ 6.5% were identified as risk factors. In a 24-month follow-up analysis, the incidence of grade ≥ 3 hyperglycemia was 4.4%, and the median time to onset of hyperglycemia was 19 days. There have been postmarketing reports of EV-induced DKA, as well as cases of refractory hyperglycemia requiring more than 1,000 units of insulin daily. The mechanism explaining the hyperglycemia is not yet defined, but in the prior case reports, as well as the current case, C-peptide levels have been elevated. It is assumed, therefore, that the mechanism involves insulin resistance as opposed to insulin deficiency. The marked hyperglycemia appears to be reversible once EV therapy is discontinued. In 2023, EV was approved in combination with pembrolizumab for first-line therapy of locally advanced or metastatic urothelial cancer, as an alternative to platinum-based chemotherapy. With this expanded indication, providers should be aware of the risk of hyperglycemia, which in some cases may be severe. Presentation: 6/3/2024

Water and Electrolyte Content in Hypertension in the Skin (WHYSKI) in Primary Aldosteronism.

Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K+ loss and enhanced Na+ reabsorption. We investigated whether the electrolyte, water, and TonEBP (tonicity-responsive enhancer binding protein)/NFAT5 (nuclear factor of activated T cells 5) content is altered in the skin of patients with PA and corrected by surgical cure. We obtained skin biopsies from 80 subjects: 49 consecutive patients with PA, optimally treated with a mineralocorticoid receptor antagonist; 6 essential hypertensives; and 25 normotensive controls. We measured Na+, K+, water content with atomic absorption spectroscopy after ashing, and NFAT5 mRNA with digital droplet polymerase chain reaction. The patients with PA were retested after adrenalectomy. We discovered a higher dry weight of the skin biopsy specimen at surgery than at follow-up (P<0.001) and a direct correlation with electrolyte and water content (all P<0.01), indicating the need for dry weight adjustment of electrolyte and water data. Surgical cure of PA markedly increased skin dry weight-adjusted K+ (from 1.14±0.1 to 2.81±0.27 µg/mg; P<0.001) and water content (from 2.92±1.4 to 3.85±0.23 mg/mg; P<0.001), but left dry weight-adjusted skin Na+ content unaffected. In patients with PA, NFAT5 mRNA was higher (P=0.031) than in normotensive controls and decreased after surgery (P=0.035). Despite mineralocorticoid receptor antagonist treatment ensuring normokalemia, the patients with PA had a skin cell K+ depletion that was corrected by adrenalectomy. The activated NFAT5/TonEBP pathway during mineralocorticoid receptor antagonist administration suggests enhanced skin Na+ lymphatic drainage and can explain the lack of overt skin Na+ accumulation in patients with PA. Its deactivation after surgical cure can account for the lack of skin Na+ decrease postadrenalectomy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06090617.

Ulcerative type 1 lepra reaction in borderline-tuberculoid leprosy

Introduction: leprosy is a chronic infectious disease caused by Mycobacterium leprae, characterized by a wide spectrum of clinical presentations. In India, borderline-tuberculoid leprosy is the most common form encountered in clinical practice. Type 1 lepra reaction in borderline- uberculoid leprosy usually presents as the development of erythema and/or edema in pre-existing skin lesions. Ulceration of skin lesions in type 1 lepra reaction is uncommon and occurs in severe reactions. Objective: to report an unusual presentation of borderline-tuberculoid leprosy with ulcerative type 1 lepra reaction in an immunocompetent patient. Case description: we present the case of a 65-yearold man with chief complaints of ulcerated plaque over his left thigh. He also had other skin lesions suggestive of borderline-tuberculoid leprosy over his trunk and limbs, as well asenlarged, mildly tender left ulnar and lateral popliteal nerves. A slit skin smear was negative, while a skin biopsy supported the diagnosis of borderline-tuberculoid leprosy. The patient responded to multibacillary multidrug therapy according recommended by World Health Organization and tapering doses of prednisolone, with complete healing of the ulceration at six weeks follow-up. Discussion: type 1 lepra reaction associated with borderline-tuberculoid leprosy usually presents with increased erythema and edema in pre-existing skin lesions. Ulceration in such skin lesions is not commonly seen except in cases with severe type 1 leprosy reactions. Administration of oral corticosteroids along with multibacillary multidrug therapy is the key to managing ulcerative type 1 lepra reaction. The ulceration heals rapidly with tapering doses of oral corticosteroids, limiting the duration of morbidity. Final consideration: the case emphasizes the need for dermatologists and leprologists to be aware of atypical presentations of leprosy reactions, ensuring timely diagnosis and effective management to achieve optimal patient outcomes.

Skin Biopsies and Diagnostic Outcomes at a Multisite Family Medicine Residency Network.

Physicians other than dermatologists evaluate nearly 60% of all skin diseases, and 22% of these physicians are family physicians. Dermatology education is therefore an important aspect of Family Medicine training. Dermatologic procedural training in Family Medicine residency is not standardized, however, so family physicians graduate with highly variable skills. This study describes the scope and diagnostic outcomes of skin biopsies performed by residents at a multisite Family Medicine residency network in comparison with those performed by attendings at a Family Medicine faculty community practice. We performed a retrospective chart review of patients evaluated at eight Family Medicine residency training sites and one Family Medicine faculty community practice within a regional academic health system between January 2020 and October 2022. Patients with a skin finding who underwent at least one skin biopsy during their visit were included in the study. Among all of the skin findings, the incidence of skin biopsy was 3.6% (258/7104) for residents and 1.8% (175/9917) for attendings (P < 0.001). Family Medicine residents performed fewer shave biopsies (57.8% vs 77.7%, P < 0.001) and more punch biopsies (25.6% vs 11.4%, P < 0.001) compared with attendings. Most biopsies performed by residents and attendings were benign, although residents biopsied significantly more benign (79.1% vs 64.6%, P < 0.001) and malignant lesions (11.2% vs 5.7%, P = 0.049). Attendings biopsied significantly more low-to-moderate-grade dysplastic (22.3% vs 5.0%, P < 0.001) and high-grade atypical lesions (4.0% vs 0.8%, P = 0.034). Family Medicine residents at this residency network receive training in a variety of skin biopsy types. Distinct skin biopsy practices and outcomes between residents and attendings may reflect differences in patient populations, clinical expertise, and dermatology referral patterns.